Dataset Information

Molecular Characterisation of the A52 Murine Hepatocellular Carcinoma Cell Line

ABSTRACT: Background: To combat hepatocellular carcinoma (HCC) disease heterogeneity and growing mortality, there is an urgent need for targeted and personalised therapeutics. While syngeneic mouse models are commonly used for preclinical validation of these therapeutics, the lack of genetically characterised murine cell lines adds uncertainty to the study of drug-gene interactions in these models. We previously generated a novel murine cell line, A52, from a diethylnitrosamine (DEN)-induced adiponectin-knockout mouse model. Here, we present a comprehensive genomic and transcriptomic characterisation of the A52 cell line. Methods: A52 cells were grown in various culture medium compositions to investigate robustness to simple media. Whole-genome sequencing (WGS) and RNAseq were performed on A52 cells from both cell culture and syngeneic tumour tissue, as well as a reference cell line representing non-tumour cells, AML-12. Results: A52 was found to show robust growth in all medium compositions. Substantial chromosomal instability was observed in A52, including trisomy 15 and notable amplifications of oncogenic loci such as Myc and Cd274 (PDL-1), alongside frequent small variants and structural rearrangements. Notably, the cell line harbours the common HCC driver Braf V584E mutation, and a novel Plk1 p.R364W variant predicted as a driver mutation. Transcriptomic profiling defined a distinct "A52 gene signature" enriched in EGFR-ERBB signalling and cell migration pathways. Integrative analyses demonstrated that the A52 gene signature aligns closely with a subset of human HCC lacking CTNNB1 mutations. Conclusion: This study provides a critical genetic resource, facilitating more precise preclinical modelling and therapeutic validation in HCC.

ORGANISM(S): Mus musculus

PROVIDER: GSE302860 | GEO | 2025/12/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:<p>Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality with limited therapies. While endoplasmic reticulum (ER)-stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR-transducer activating transcription factor 6 alpha (ATF6α) remains unclear. In contrast to the well-characterized role of ATF6α-activation as an adaptive response to ER-stress, we demonstrate its hitherto unknown function as an ER-stress-inducing tumor-driver and metabolic master-regulator restricting cancer-immunosurveillance for HCC. ATF6α-activation in human HCC significantly correlated with an aggressive phenotype characterized by reduced patient-survival, enhanced tumor-progression, and local immunosuppression. Hepatocyte-specific ATF6α-activation in mice induced progressive hepatitis with ER-stress, immunosuppression, and hepatocyte-proliferation. Concomitantly, activated-ATF6α increased glycolysis and directly repressed gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) by binding to gene regulatory elements. Restoring FBP1 expression prevented ATF6α-activation-related pathologies. Prolonged ATF6α-activation in hepatocytes triggered hepatocarcinogenesis, intratumoral T-cell infiltration, and nutrient-deprived immune-exhaustion. Immune-checkpoint blockade (ICB) efficiently restored immunosurveillance and dramatically reduced HCC. In line, HCC patients achieving complete response to immunotherapy displayed significantly increased ATF6α-activation compared to those with a weaker response. Targeting Atf6 via germline, hepatocyte-specific ablation, or therapeutic hepatocyte delivery of antisense-oligonucleotides dampened HCC in preclinical liver-cancer models. Thus, prolonged ATF6α-activation drives ER-stress, leading to glycolysis-dependent immunosuppression in liver cancer, sensitizing to ICB. Our findings suggest persistently activated ATF6α is a tumor-driver, a potential stratification-marker for ICB response and a therapeutic target in HCC.</p>

Dataset Information

Molecular Characterisation of the A52 Murine Hepatocellular Carcinoma Cell Line

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets